Naringin promotes osteogenesis and ameliorates osteoporosis development by targeting JAK2/STAT3 signalling

Abstract

Osteoporosis is a systemic bone metabolism disorder, which increases the risk of fractures, and in severe cases it may cause disability or even death. An important factor contributing to osteoporosis is the imbalance between bone formation and resorption. Naringin was reported to promote osteoblast differentiation, thus enhancing bone formation and alleviating osteoporosis development. However, the signalling pathways related to the regulatory mechanism of naringin in osteoporosis development are not clear. Proliferation of bone mesenchymal stem cells (BMSCs) treated with naringin in vitro was detected by CCK-8. An osteogenesis differentiation medium supplemented with naringin was applied to explore the effects of naringin on BMSC osteogenic differentiation, as detected by Alizarin red staining. Ovariectomy (OVX)induced postmenopausal osteoporosis (PMOP) rats were orally administered with naringin. Dual-energy X-ray absorptiometry (DEXA) and micro-CT were applied to measure bone mineral density (BMD), bone volume/total volume (BV/TV), trabecula thickness (Tb.Th), trabecula number (Tb.N), trabecular separation (Tb.Sp) and bone surface/bone volume (BS/BV). H&E staining was performed to show pathological changes of the femur in PMOP rats after naringin treatment. Bone metabolism indicators were assessed by ELISA. We found that naringin suppressed the activation of the JAK2/STAT3 pathway. Naringin promoted BMSC proliferation and osteogenic differentiation. Furthermore, naringin alleviates bone loss and improves abnormal bone metabolism of PMOP rats. Collectively, naringin promotes BMSC osteogenic differentiation to ameliorate osteoporosis development by targeting JAK2/STAT3 signalling.

The Development of Naringin for Use against Bone and Cartilage Disorders

“…Naringin may significantly improve BMSC viability and osteogenic differentiation by suppressing JAK2/STAT3 signaling. In OVX-induced rat postmenopausal OP, naringin exhibits similar effects to AG490 (an inhibitor of JAK2/STAT3 signaling) to improve the bone parameters from dual-energy X-ray absorptiometry and micro-CT and suppresses the development of OP [101]. These results consistently support the finding that naringin ameliorates OVX-induced rat bone loss, increases the expression of osteocalcin, and promotes the osteogenic differentiation of BMSCs [102].…”

STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis

“…These effects were abrogated by a JAK2/STAT3 inhibitor (AG490), which indicated that EPO significantly stimulated osteoblast proliferation and differentiation via the JAK2/STAT3 pathway [ 70 ]. Naringin, which is the main active ingredient of Chinese herbal medicines, facilitates BMSC proliferation and osteogenic differentiation by inhibiting the JAK2/STAT3 pathway and alleviates bone loss in an ovariectomy (OVX)-induced postmenopausal osteoporosis (PMOP) rat model [ 71 ]. Thus far, studies have focused on the role of STAT3 in bone development and bone homeostasis, particularly in response certain stimuli, and a potential treatment strategy or agent showed inconsistent results in terms of the activation of STAT3 and the effect on bone or osteoblast lineage cells, which indicates a nonspecific role of STAT3 in osteogenesis.…”

Three‐dimensional starch‐based scaffold decorated with 64S bio‐glass for accelerating rat model bone defect repair

“…demonstrated that osteoporosis is encouraged by the initiation and expansion of the Janus activated kinase 2 (JAK2)/signal transducer and the activator of transcription 3 (STAT3) pathway 105 . In confirmation, it was found that naringin can cause osteogenesis through preventing the onset and development of the JAK2/STAT3 pathway 104 . Masson's staining demonstrated that the S7 scaffold was much more successful and efficient in accelerating and inducing the healing process of skull defect compared to the control group.…”

“…According to obtained results, researchers claimed that the hybrid's high ability to repair rat bone defect is attributed to the osteogenic properties of naringin 103 . Recently, the mechanism by which naringin stimulates bone formation and prevents osteoporosis has been investigated 104 . In their investigations, Wang et al.…”

“…103 Recently, the mechanism by which naringin stimulates bone formation and prevents osteoporosis has been investigated. 104 In their investigations, Wang et al demonstrated that osteoporosis is encouraged by the initiation and expansion of the Janus activated kinase 2 (JAK2)/signal transducer and the activator of transcription 3 (STAT3) pathway. 105 In confirmation, it was found that naringin can cause osteogenesis through preventing the onset and development of the JAK2/STAT3 pathway.…”